Basement membrane components in cutaneous neurofibroma of von Recklinghausen's disease.
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Basement Membrane↗
Biomedical subjects
T Krieg
Publications and source records attributed to T Krieg.
Collagen type distribution and macromolecular organization of connective tissue in different layers of human skin.
Human skin is composed of several layers which are characterized by a specific macromolecular organization of connective tissue. Three approaches were used to quantify the collagen types present in each of the different layers: biochemical analysis of authentic tissue, metabolic labeling of organ cultures, and metabolic labeling of fibroblast monolayers. We obtained reproducible evidence for a somewhat higher ratio of type III/type I collagen synthesis in the papillary dermis and the subcutaneous fat compared to the reticular layer. Constant amounts of alpha 1 (I) trimers and type V collagen were found in all layers. The degree of hydroxylation of lysine in either type I or type III collagen was the same in any layer of the skin.
Adipose Tissue↗
Ultrastructure and composition of connective tissue in hyalinosis cutis et mucosae skin.
Skin biopsies from a patient with hyalinosis cutis et mucosae (HCM) were studied by routine histology, electron microscopy, biochemical extractions, and immunofluorescence for extracellular matrix proteins. The upper dermis consisted of large hyaline regions mainly composed of noncollagenous proteins. A portion of this material was solubilized by reduction in 8 M urea. Anti-sera against these proteins revealed multiple antigens most of which were also detectable in normal skin. The hyaline regions showed a reduced content of collagens, particularly of thick fibrils and of fibronectin. The basal lamina around capillaries and at the dermal-epidermal junction appeared as multiple, concentric layers of amorphous laminae intercalated with thin collagen fibrils. They consisted of collagens type III and IV and of laminin as shown by immunofluorescence. Antibodies could also be raised against laminin of HCM skin which showed strong cross-reactions with authentic mouse laminin. Cultured fibroblasts from the HCM lesion showed increased synthesis of noncollagenous proteins at the expense of newly synthesized collagens. Some but not all of these noncollagenous proteins were also produced by fibroblasts from normal skin. The above data indicate that the hyaline material in HCM originates from the overproduction of noncollagenous proteins, most of which are normal constituents of human skin.
Adult↗
Ehlers-Danlos syndrome type VI: collagen type specificity of defective lysyl hydroxylation in various tissues.
The Ehlers-Danlos syndrome type VI is an inherited disorder of collagen metabolism characterized by a defective lysyl hydroxylase. The resulting lack of hydroxylysine has been found in several connective tissues, all of which show varying degrees of clinical symptoms. In the present study, collagen was isolated from different connective tissues and the degree of hydroxylation of lysyl residues was determined. Subsequently, collagen types I, II, III, IV, and V have been prepared from a number of tissues. Insufficient hydroxylation of lysyl residues was found in type I and type III collagen, whereas types II, IV, and V showed normal amounts of hydroxylysine. The expression of the defect, even for type I and type III collagen, varied widely from one tissue to another. A complete lack of hydroxylysine was observed in skin, while it was less pronounced in tissues such as bone, tendon, lung, or kidney. The data suggest the presence of several isoenzymes having varying affinities to the different collagen types.
Adult↗
Effect of vitamin A and its derivatives on collagen production and chemotactic response of fibroblasts.
Vitamin A and several other retinoids were added to fibroblast cultures in order to study possible alterations in biochemical properties and cellular responsiveness. The proliferation of cells was inhibited as the concentration of retinoids increased from 10(-9) to 10(-5) mol/l. Synthesis of non-collagenous proteins and production of both type I and type III collagen were decreased. The onset of type III collagen synthesis by tendon fibroblasts in culture was delayed. Furthermore, the chemotactic response of fibroblasts to fibroblast-conditioned medium was markedly reduced in the presence of retinoids (10(-6) to 10(-12) mol/l).
Acitretin↗
Basement membrane components outline the tumour islands in cylindroma.
The main histological feature of cylindroma is the deposition of sheaths of a 'hyalinized' material contiguous to the tumour cell clusters. Although ultrastructural studies of this material have revealed a basement membrane-like structure, its exact nature has remained unclear. Using immuno-staining with affinity-purified antibodies directed against distinct basement membrane components, we have shown that type IV collagen and laminin are major constituents of this zone. In addition, cell culture studies indicated that both proteins are synthesized by the tumour cells. The immunohistological data make it clear that the tumour matrix between the tumour cell islands is composed not only of basement membrane components, but also is composed of other connective tissue constituents, i.e. type I and III collagen and fibronectin.
Basement Membrane↗
Congenital fascial dystrophy--a noninflammatory disease of fascia: the stiff skin syndrome.
Our patient's disease was similar to the persons with stiff skin syndrome described by Esterly and McKusick (1). Stony-hard indurations of the skin and deeper tissue were generalized but most pronounced in the buttocks, thighs, and legs, with limitation of joint mobility and particularly extensive contractures in the lower limbs. The disease was noticed when the patient was 18 months old, and was nonprogressive within a follow-up period of 12 years. There was no visceral involvement except functional impairment of the lungs, probably due to thickened thoracic fascia. Biochemical, histologic, and electron microscopic studies of the skin and muscle were not remarkable. In skin fibroblasts, collagen synthesis was increased and was accompanied by elevated activity of the prolylhydroxylase and lysylhydroxylase, whereas the transferases were not altered. The fascia was considerably thickened, but contained no inflammatory infiltrates. The significant electron microscopic finding was the presence of amianthoid-like collagen fibers in the fascia.
Biopsy↗
[Basement membranes--structure, function, pathology].
Basement membranes are extracellular structures with a heterogeneous molecular composition. Several components have been identified and could be localized in specific morphological structures. Type IV collagen is found in the lamina densa, whereas laminin is the major component of the lamina lucida. Small amounts of heparan sulfate proteoglycan are also present in the lamina lucida. In some basement membranes, fibronectin and another glycoprotein, nidogen, could be identified. Epidermal basement membranes contain, in addition, the bullous pemphigoid antigen. Basement membranes are involved in several diseases and play an important part in tumor progression. Antibodies against distinct components of basement membranes have been shown to be useful as diagnostic tools in bullous disorders (e.g., epidermolysis bullosa) and for identifying the extracellular matrix of skin tumors (e.g., neurofibroma, cylindroma, granular cell myoblastoma).
Basement Membrane↗
[Cutis hyperelastica circumscripta. A case report with a morphologic study].
This is a report on a 20-year-old female patient with localized cutis hyperelastica. Light and electron microscopy revealed an increase of elastic fibers compared to collagen tissue.
Adult↗
[Cutis laxa. Classification, clinical aspects and molecular defects].
Cutis laxa summarizes a heterogeneous group of diseases which are characterized by loose skin. An additional to the clinical variants of cutis laxa, a brief review of the elastin pathway is given and possible defects in cutis laxa are discussed.
Adult↗
Analysis of cyanogen bromide peptides of type I collagen from a patient with lethal osteogenesis imperfecta.
The CNBr peptides of type I collagen from bone of a patient with lethal osteogenesis imperfecta and age-matched controls were isolated by molecular-sieve chromatography and their amino acid compositions were determined. No differences were found between the compositions of the peptides from the patient and those from the controls, except for an increase in the degree of hydroxylation of lysine in all peptides from the patient. Type I collagen CNBr peptides from chick-embryo skin [Barnes, Constable Morton & Kodicek (1971) Biochem. J. 125, 925--928] and guinea-pig scar tissue [Shuttleworth, Forrest & Jackson (1975) Biochim. Biophys. Acta 379, 207--216] also have an increased degree of hydroxylation of lysine with an otherwise normal amino acid composition, and it was believed that this could be an embryonic form of collagen. As a similar collagen was present in the bones of the patient studied, it seems possible that the same 'embryonic' collagen is synthesized during development, in repair process and also in genetic disorders of collagen metabolism.
Amino Acids↗
Collagen synthesis in generalized morphea.
Synthesis of collagen and non-collagenous proteins was measured in fibroblast cultures derived from different layers of the dermis from a patient with an early stage of localized scleroderma. Increased synthesis of collagen was found in fibroblasts grown from the subcutaneous fat of this patient, whereas cells obtained from the papillary dermis revealed normal metabolism. These data agree with the results obtained in previous experiments with cells derived from patients with progressive systemic sclerosis in primary culture, thus indicating that the two diseases have a common pathomechanism. Several subcultures of the activated fibroblast populations were also studied. Normal collagen synthesis in these cultures was observed after the fifth passage, probably indicating selection of cell populations or loss of the previous phenotype.
Adipose Tissue↗
Biochemical investigation of cells from keratoconus and normal cornea.
Collagen is the major structural protein in the cornea. In keratoconus the central cornea is thin, opaque and weak. Collagen synthesis was investigated in cells derived from the stroma of cornea with keratoconus and from controls. No difference was found in the ratio of collagens type I and type III synthesized, which were investigated as procollagens and after conversion to collagen as well. The alpha 1/alpha 2 ratio in type I collagen was similar in keratoconus cells and controls.
Cells, Cultured↗
Serum and urine analysis of the aminoterminal procollagen peptide type III by radioimmunoassay with antibody Fab fragments.
A radioimmunoassay based on antibody Fab fragments was developed for the aminoterminal peptide Col 1-3 of bovine type III procollagen. This assay does not distinguish the intact aminopropeptide Col 1-3 from its globular fragment Col 1. Parallel inhibition profiles were observed with human serum and urine allowing the simultaneous quantitative determination of intact and fragmented antigens in these samples. Most of the material has a size similar to that of fragment Col 1 indicating that the aminopropeptide is degraded under physiologic conditions. The concentration of aminopeptide in normal sera was in the range 15-63 ng/ml. Daily excretion was found to be in the range 30-110 micrograms. More than 50% of patients with alcoholic hepatitis and liver cirrhosis showed elevated serum levels of aminopropeptide by the Fab assay. Elevated concentrations were detected more frequently with an antibody radioimmunoassay which measures mainly the intact form of the aminopropeptide. It is suggested that analysis of patients material by both assays could improve their diagnostic application.
Adolescent↗
Biochemical characterization of variants of the Ehlers-Danlos syndrome type VI.
Three variants of the Ehlers-Danlos syndrome type VI are described: a severe form with skeletal, dermal and ocular manifestations associated with a lack of hydroxylysine in skin and little lysyl hydroxylase activity in cultured fibroblasts; a similarly affected form with a nearly normal hydroxylsine content in skin, but with only little enzyme activity in cultured fibroblasts; and a predominantly ocular form with no biochemical abnormality in skin or cultured skin fibroblasts. The activities of prolyl 4-hydroxylase and the two hydroxylysyl glycosyltransferases were normal in all cases, and the failure to find lysyl hydroxylase activity was not due to altered solubility characteristics of the enzyme or to the presence of an enzyme inhibitor. The collagen produced in cell culture, however, was hydroxylated to a markedly higher extent than that found in skin. In both the mutant and control cells hydroxylation of lysyl residues was less sensitive to ascorbate deficiency than that of prolyl residues.
Adolescent↗
(+)-Cyanidanol-3 changes functional properties of collagen.
About 6-7 (+)-cyanidanol-3 molecules are bound per collagen alpha-chain. The (+)-cyanidanol-3 treated collagen contains an increased number of pepsin-resistant cross-links, is less susceptible to attack by mammalian collagenase, has a higher shrinkage temp and forms unstructured aggregates. Cell and organ culture studies show that these biological systems produce less protein and collagen in the presence of (+)-cyanidanol-3 and that the newly synthesized collagen is less soluble.
Benzopyrans↗
Influence of cell density on collagen biosynthesis in fibroblast cultures.
Characteristic features of collagen metabolism in human skin fibroblasts were studied in relation to cell density. Measuring peptide-bound hydroxyproline we found that collagen synthesis per cell decreased when cultures approached confluency. On the other hand, the relative rate of collagen synthesis (collagen/total protein) was higher in quiescent than in proliferating cultures. With increasing cell density the proportion of type III collagen in comparison with type I was found to be slightly increased. In addition, in low-density cultures [alpha I(I)]3 collagen trimers were produced in considerable amounts, whereas they were no longer detected in cultures with a high cell density. Although hydroxylation of proline residues was normal in all cell stages, conversion of procollagen into collagen was found to depend strongly on the density at which the cells were investigated. Almost no cleavage of procollagen peptides was observed in rapidly growing cells, whereas highly confluent cell cultures converted most of the newly synthesized procollagen molecules.
Cell Count↗
Low rate of procollagen conversion in dermatosparactic sheep fibroblasts is paralleled by increased synthesis of type I and type III collagens.
Dermatosparaxis is a genetic defect found in humans and animals, which affects the conversion of procollagen to collagen and aminopropeptides . Under cell culture conditions a reduction of the release of aminopropeptides is paralleled by an increased synthesis of collagens type I and III. This fact provides further evidence for a regulatory involvement of aminopropeptides in the biosynthesis of collagen.
Animals↗